Nita Shrikant Kulkarni, MD

Clinical question

As compared with crystalloid therapy, does the use of colloid solutions for fluid resuscitation in the intensive care unit improve mortality in critically ill patients with hypovolemic shock?

Bottom line

For critically ill patients with acute hypovolemic shock, the use of colloid solutions for fluid resuscitation does not significantly affect short-term mortality as compared with the use of crystalloid solutions. However, the data suggest that deaths over 90 days may be reduced with colloids. More research is needed to confirm these findings. (LOE = 1b-)

Reference

Annane D, Siami S, Jaber S, et al, for the CRISTAL Investigators. Effects of fluid resuscitation with colloids vs crystalloids on mortality in critically ill patients presenting with hypovolemic shock. JAMA 2013:310(17);1809-1817.

Study design

Randomized controlled trial (nonblinded)

Funding source

Government

Allocation

Concealed

Setting

Inpatient (ICU only)

Synopsis

Critically ill patients with acute hypovolemia were randomized, using concealed allocation, to receive fluid resuscitation with crystalloids or colloids. Patients who had already received fluid resuscitation while in the intensive care unit (ICU) were excluded from the study. Randomization was stratified according to diagnosis: sepsis, trauma, or other causes of hypovolemic shock. In the crystalloid group, patients received isotonic or hypertonic saline or other buffered solutions; patients in the colloid group received hypo- or hyper-oncotic solutions such as gelatins, dextrans, hydroxyethyl starches, or albumin. The amount and duration of fluid resuscitation was left to the discretion of the clinicians. Clinicians were not masked as it was considered infeasible to stock the units with adequately masked fluid solutions, especially for the use in emergencies. Analysis was by intention to treat. Baseline characteristics in the 2 groups were similar. The median age was 63 years and the majority of patients had hypovolemia due to sepsis. The median volume of fluid administered (excluding maintenance therapy) during the first 7 days in the ICU was higher in the crystalloid group (3 L vs 2 L; P < .001). For the primary outcome of mortality at 28 days, there was no significant difference detected between the 2 groups. Although there were fewer deaths in the colloid group at 90 days, this was a secondary outcome and the confidence interval approached 1 (31% vs. 34%; relative risk = 0.92; 95% CI, 0.86-0.99; P = .03). At the 28-day mark, patients in the colloid group were more likely to be alive without the need for mechanical ventilation (14.6 days vs 13.5 days; P = .01) or vasopressor therapy (16.2 days vs 15.2 days; P = .03).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

As compared with crystalloid therapy, does the use of colloid solutions for fluid resuscitation in the intensive care unit improve mortality in critically ill patients with hypovolemic shock?

Bottom line

For critically ill patients with acute hypovolemic shock, the use of colloid solutions for fluid resuscitation does not significantly affect short-term mortality as compared with the use of crystalloid solutions. However, the data suggest that deaths over 90 days may be reduced with colloids. More research is needed to confirm these findings. (LOE = 1b-)

Reference

Annane D, Siami S, Jaber S, et al, for the CRISTAL Investigators. Effects of fluid resuscitation with colloids vs crystalloids on mortality in critically ill patients presenting with hypovolemic shock. JAMA 2013:310(17);1809-1817.

Study design

Randomized controlled trial (nonblinded)

Funding source

Government

Allocation

Concealed

Setting

Inpatient (ICU only)

Synopsis

Critically ill patients with acute hypovolemia were randomized, using concealed allocation, to receive fluid resuscitation with crystalloids or colloids. Patients who had already received fluid resuscitation while in the intensive care unit (ICU) were excluded from the study. Randomization was stratified according to diagnosis: sepsis, trauma, or other causes of hypovolemic shock. In the crystalloid group, patients received isotonic or hypertonic saline or other buffered solutions; patients in the colloid group received hypo- or hyper-oncotic solutions such as gelatins, dextrans, hydroxyethyl starches, or albumin. The amount and duration of fluid resuscitation was left to the discretion of the clinicians. Clinicians were not masked as it was considered infeasible to stock the units with adequately masked fluid solutions, especially for the use in emergencies. Analysis was by intention to treat. Baseline characteristics in the 2 groups were similar. The median age was 63 years and the majority of patients had hypovolemia due to sepsis. The median volume of fluid administered (excluding maintenance therapy) during the first 7 days in the ICU was higher in the crystalloid group (3 L vs 2 L; P < .001). For the primary outcome of mortality at 28 days, there was no significant difference detected between the 2 groups. Although there were fewer deaths in the colloid group at 90 days, this was a secondary outcome and the confidence interval approached 1 (31% vs. 34%; relative risk = 0.92; 95% CI, 0.86-0.99; P = .03). At the 28-day mark, patients in the colloid group were more likely to be alive without the need for mechanical ventilation (14.6 days vs 13.5 days; P = .01) or vasopressor therapy (16.2 days vs 15.2 days; P = .03).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

As compared with crystalloid therapy, does the use of colloid solutions for fluid resuscitation in the intensive care unit improve mortality in critically ill patients with hypovolemic shock?

Bottom line

For critically ill patients with acute hypovolemic shock, the use of colloid solutions for fluid resuscitation does not significantly affect short-term mortality as compared with the use of crystalloid solutions. However, the data suggest that deaths over 90 days may be reduced with colloids. More research is needed to confirm these findings. (LOE = 1b-)

Reference

Annane D, Siami S, Jaber S, et al, for the CRISTAL Investigators. Effects of fluid resuscitation with colloids vs crystalloids on mortality in critically ill patients presenting with hypovolemic shock. JAMA 2013:310(17);1809-1817.

Study design

Randomized controlled trial (nonblinded)

Funding source

Government

Allocation

Concealed

Setting

Inpatient (ICU only)

Synopsis

Critically ill patients with acute hypovolemia were randomized, using concealed allocation, to receive fluid resuscitation with crystalloids or colloids. Patients who had already received fluid resuscitation while in the intensive care unit (ICU) were excluded from the study. Randomization was stratified according to diagnosis: sepsis, trauma, or other causes of hypovolemic shock. In the crystalloid group, patients received isotonic or hypertonic saline or other buffered solutions; patients in the colloid group received hypo- or hyper-oncotic solutions such as gelatins, dextrans, hydroxyethyl starches, or albumin. The amount and duration of fluid resuscitation was left to the discretion of the clinicians. Clinicians were not masked as it was considered infeasible to stock the units with adequately masked fluid solutions, especially for the use in emergencies. Analysis was by intention to treat. Baseline characteristics in the 2 groups were similar. The median age was 63 years and the majority of patients had hypovolemia due to sepsis. The median volume of fluid administered (excluding maintenance therapy) during the first 7 days in the ICU was higher in the crystalloid group (3 L vs 2 L; P < .001). For the primary outcome of mortality at 28 days, there was no significant difference detected between the 2 groups. Although there were fewer deaths in the colloid group at 90 days, this was a secondary outcome and the confidence interval approached 1 (31% vs. 34%; relative risk = 0.92; 95% CI, 0.86-0.99; P = .03). At the 28-day mark, patients in the colloid group were more likely to be alive without the need for mechanical ventilation (14.6 days vs 13.5 days; P = .01) or vasopressor therapy (16.2 days vs 15.2 days; P = .03).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

Does the use of renal artery stenting combined with aggressive medical therapy improve outcomes in patients with severe atherosclerotic renal artery stenosis?

Bottom line

In patients with severe atherosclerotic renal artery stenosis and hypertension or chronic kidney disease, renal artery stenting does not provide an additional benefit when added to comprehensive medical therapy that includes blood pressure and diabetes management and antiplatelet and lipid therapies. (LOE = 1b)

Reference

Cooper CJ, Murphy TP, Cutlip DE, et al. Stenting and medical therapy for atherosclerotic renal-artery stenosis. N Engl J Med. 2013 Nov 13 [Epub ahead of print].

Study design

Randomized controlled trial (nonblinded)

Funding source

Industry + govt

Allocation

Concealed

Setting

Outpatient (any)

Synopsis

These investigators enrolled 947 patients with severe atherosclerotic renal artery stenosis (60% stenosis or more). Eligible patients also had either systolic hypertension while taking 2 or more antihypertensive medications or chronic kidney disease. Using concealed allocation, patients were randomized to receive either stenting plus medical therapy or medical therapy alone. Medical management included antiplatelet agents, antihypertensives, and lipid-lowering therapies. Specifically, all patients received candesartan with or without hydrochorthiazide, as well as the combination pill amlodipine-atorvastatin. Diabetes was managed according to clinical practice guidelines. The 2 groups had similar comorbidities at baseline. Overall, 90% of patients in each group had hyperlipidemia and approximately 30% had diabetes. The primary outcome was a composite of death from cardiovascular or renal causes, stroke, myocardial infarction, hospitalization for acute heart failure, worsening renal insufficiency, or the need for permanent dialysis. At a median follow-up of 43 months, there was no significant difference detected between the 2 groups in either the composite outcome (hazard ratio [HR] = 0.95; 95% CI, 0.76-1.17) or its individual components. All-cause mortality was also similar (HR = 0.80; 0.58-1.12).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

Does the use of renal artery stenting combined with aggressive medical therapy improve outcomes in patients with severe atherosclerotic renal artery stenosis?

Bottom line

In patients with severe atherosclerotic renal artery stenosis and hypertension or chronic kidney disease, renal artery stenting does not provide an additional benefit when added to comprehensive medical therapy that includes blood pressure and diabetes management and antiplatelet and lipid therapies. (LOE = 1b)

Reference

Cooper CJ, Murphy TP, Cutlip DE, et al. Stenting and medical therapy for atherosclerotic renal-artery stenosis. N Engl J Med. 2013 Nov 13 [Epub ahead of print].

Study design

Randomized controlled trial (nonblinded)

Funding source

Industry + govt

Allocation

Concealed

Setting

Outpatient (any)

Synopsis

These investigators enrolled 947 patients with severe atherosclerotic renal artery stenosis (60% stenosis or more). Eligible patients also had either systolic hypertension while taking 2 or more antihypertensive medications or chronic kidney disease. Using concealed allocation, patients were randomized to receive either stenting plus medical therapy or medical therapy alone. Medical management included antiplatelet agents, antihypertensives, and lipid-lowering therapies. Specifically, all patients received candesartan with or without hydrochorthiazide, as well as the combination pill amlodipine-atorvastatin. Diabetes was managed according to clinical practice guidelines. The 2 groups had similar comorbidities at baseline. Overall, 90% of patients in each group had hyperlipidemia and approximately 30% had diabetes. The primary outcome was a composite of death from cardiovascular or renal causes, stroke, myocardial infarction, hospitalization for acute heart failure, worsening renal insufficiency, or the need for permanent dialysis. At a median follow-up of 43 months, there was no significant difference detected between the 2 groups in either the composite outcome (hazard ratio [HR] = 0.95; 95% CI, 0.76-1.17) or its individual components. All-cause mortality was also similar (HR = 0.80; 0.58-1.12).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

Does the use of renal artery stenting combined with aggressive medical therapy improve outcomes in patients with severe atherosclerotic renal artery stenosis?

Bottom line

In patients with severe atherosclerotic renal artery stenosis and hypertension or chronic kidney disease, renal artery stenting does not provide an additional benefit when added to comprehensive medical therapy that includes blood pressure and diabetes management and antiplatelet and lipid therapies. (LOE = 1b)

Reference

Cooper CJ, Murphy TP, Cutlip DE, et al. Stenting and medical therapy for atherosclerotic renal-artery stenosis. N Engl J Med. 2013 Nov 13 [Epub ahead of print].

Study design

Randomized controlled trial (nonblinded)

Funding source

Industry + govt

Allocation

Concealed

Setting

Outpatient (any)

Synopsis

These investigators enrolled 947 patients with severe atherosclerotic renal artery stenosis (60% stenosis or more). Eligible patients also had either systolic hypertension while taking 2 or more antihypertensive medications or chronic kidney disease. Using concealed allocation, patients were randomized to receive either stenting plus medical therapy or medical therapy alone. Medical management included antiplatelet agents, antihypertensives, and lipid-lowering therapies. Specifically, all patients received candesartan with or without hydrochorthiazide, as well as the combination pill amlodipine-atorvastatin. Diabetes was managed according to clinical practice guidelines. The 2 groups had similar comorbidities at baseline. Overall, 90% of patients in each group had hyperlipidemia and approximately 30% had diabetes. The primary outcome was a composite of death from cardiovascular or renal causes, stroke, myocardial infarction, hospitalization for acute heart failure, worsening renal insufficiency, or the need for permanent dialysis. At a median follow-up of 43 months, there was no significant difference detected between the 2 groups in either the composite outcome (hazard ratio [HR] = 0.95; 95% CI, 0.76-1.17) or its individual components. All-cause mortality was also similar (HR = 0.80; 0.58-1.12).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

What type of venous access -- central or peripheral -- is better for patients in the intensive care unit who have no absolute indication for central access?

Bottom line

As compared with central venous catheters (CVCs), the initial use of peripheral venous catheters (PVCs) in patients in the intensive care unit (ICU) leads to more complications, primarily related to the difficulty in inserting of these catheters. Furthermore, the majority of patients in the PVC group may eventually require a CVC because of an increase in the rate of venotoxic drug infusions or because they have difficulty maintaining the PVC. (LOE = 1b-)

Reference

Ricard J, Salomon L, Boyer A, et al. Central or peripheral catheters for initial venous access of ICU patients. Crit Care Med 2013;41(9):2108-2115.

Study design

Randomized controlled trial (nonblinded)

Funding source

Government

Allocation

Concealed

Setting

Inpatient (ICU only)

Synopsis

Using concealed allocation, these investigators randomized ICU patients requiring venous access to receive either a CVC or PVC. Only patients without any absolute indications for CVCs were included. CVCs could be inserted into jugular, subclavian, or femoral sites at the discretion of the clinician. PVCs were 18-gauge or 20-gauge short catheters. Patients with a predefined increase in the rate of venotoxic drug infusions or those with difficulty maintaining a PVC were able to cross-over to the CVC group. More than half the patients in the PVC group ultimately received a CVC. Baseline characteristics were comparable between the 2 groups, with a mean age of 64 years, similar predicted mortality scores, and the majority of patients requiring mechanical ventilation. The primary outcome was the number of catheter-related complications defined as major mechanical, maintenance-related, infectious, or thrombotic complications. The determination of what constituted a major or minor complication was made a priori by the investigators. They also used a validated classification system of adverse events that rated the complications from grade 1 (minimal symptoms) to grade 5 (death). For example, one major mechanical CVC complication was the need to change insertion site, whereas a major mechanical PVC complication was needing more than 5 attempts to place a PVC. Overall, the PVC group had a greater number of major complications (133 vs 87; P = .02), the majority of which were PVC insertion difficulties (n = 56), erythema at insertion site (n = 20), and subcutaneous diffusion (n = 19). None were life threatening. When the complications were categorized using the grading classification, there were again more complications per patient in the PVC group (1.54 vs 0.89; P = .0001), mainly due to a larger number of grade 1 and grade 2 complications. Finally, more time was spent by doctors and nurses in managing catheters in the PVC group.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

What type of venous access -- central or peripheral -- is better for patients in the intensive care unit who have no absolute indication for central access?

Bottom line

As compared with central venous catheters (CVCs), the initial use of peripheral venous catheters (PVCs) in patients in the intensive care unit (ICU) leads to more complications, primarily related to the difficulty in inserting of these catheters. Furthermore, the majority of patients in the PVC group may eventually require a CVC because of an increase in the rate of venotoxic drug infusions or because they have difficulty maintaining the PVC. (LOE = 1b-)

Reference

Ricard J, Salomon L, Boyer A, et al. Central or peripheral catheters for initial venous access of ICU patients. Crit Care Med 2013;41(9):2108-2115.

Study design

Randomized controlled trial (nonblinded)

Funding source

Government

Allocation

Concealed

Setting

Inpatient (ICU only)

Synopsis

Using concealed allocation, these investigators randomized ICU patients requiring venous access to receive either a CVC or PVC. Only patients without any absolute indications for CVCs were included. CVCs could be inserted into jugular, subclavian, or femoral sites at the discretion of the clinician. PVCs were 18-gauge or 20-gauge short catheters. Patients with a predefined increase in the rate of venotoxic drug infusions or those with difficulty maintaining a PVC were able to cross-over to the CVC group. More than half the patients in the PVC group ultimately received a CVC. Baseline characteristics were comparable between the 2 groups, with a mean age of 64 years, similar predicted mortality scores, and the majority of patients requiring mechanical ventilation. The primary outcome was the number of catheter-related complications defined as major mechanical, maintenance-related, infectious, or thrombotic complications. The determination of what constituted a major or minor complication was made a priori by the investigators. They also used a validated classification system of adverse events that rated the complications from grade 1 (minimal symptoms) to grade 5 (death). For example, one major mechanical CVC complication was the need to change insertion site, whereas a major mechanical PVC complication was needing more than 5 attempts to place a PVC. Overall, the PVC group had a greater number of major complications (133 vs 87; P = .02), the majority of which were PVC insertion difficulties (n = 56), erythema at insertion site (n = 20), and subcutaneous diffusion (n = 19). None were life threatening. When the complications were categorized using the grading classification, there were again more complications per patient in the PVC group (1.54 vs 0.89; P = .0001), mainly due to a larger number of grade 1 and grade 2 complications. Finally, more time was spent by doctors and nurses in managing catheters in the PVC group.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

What type of venous access -- central or peripheral -- is better for patients in the intensive care unit who have no absolute indication for central access?

Bottom line

As compared with central venous catheters (CVCs), the initial use of peripheral venous catheters (PVCs) in patients in the intensive care unit (ICU) leads to more complications, primarily related to the difficulty in inserting of these catheters. Furthermore, the majority of patients in the PVC group may eventually require a CVC because of an increase in the rate of venotoxic drug infusions or because they have difficulty maintaining the PVC. (LOE = 1b-)

Reference

Ricard J, Salomon L, Boyer A, et al. Central or peripheral catheters for initial venous access of ICU patients. Crit Care Med 2013;41(9):2108-2115.

Study design

Randomized controlled trial (nonblinded)

Funding source

Government

Allocation

Concealed

Setting

Inpatient (ICU only)

Synopsis

Using concealed allocation, these investigators randomized ICU patients requiring venous access to receive either a CVC or PVC. Only patients without any absolute indications for CVCs were included. CVCs could be inserted into jugular, subclavian, or femoral sites at the discretion of the clinician. PVCs were 18-gauge or 20-gauge short catheters. Patients with a predefined increase in the rate of venotoxic drug infusions or those with difficulty maintaining a PVC were able to cross-over to the CVC group. More than half the patients in the PVC group ultimately received a CVC. Baseline characteristics were comparable between the 2 groups, with a mean age of 64 years, similar predicted mortality scores, and the majority of patients requiring mechanical ventilation. The primary outcome was the number of catheter-related complications defined as major mechanical, maintenance-related, infectious, or thrombotic complications. The determination of what constituted a major or minor complication was made a priori by the investigators. They also used a validated classification system of adverse events that rated the complications from grade 1 (minimal symptoms) to grade 5 (death). For example, one major mechanical CVC complication was the need to change insertion site, whereas a major mechanical PVC complication was needing more than 5 attempts to place a PVC. Overall, the PVC group had a greater number of major complications (133 vs 87; P = .02), the majority of which were PVC insertion difficulties (n = 56), erythema at insertion site (n = 20), and subcutaneous diffusion (n = 19). None were life threatening. When the complications were categorized using the grading classification, there were again more complications per patient in the PVC group (1.54 vs 0.89; P = .0001), mainly due to a larger number of grade 1 and grade 2 complications. Finally, more time was spent by doctors and nurses in managing catheters in the PVC group.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

Does the addition of colchicine improve outcomes in the treatment of an initial episode of acute pericarditis?

Bottom line

When used in addition to conventional anti-inflammatory therapy, colchicine decreases the rate of incessant or recurrent pericarditis. You would need to treat 4 patients with colchicine to prevent one such episode. (LOE = 1b)

Reference

Imazio M, Brucato A, Cemin R, et al, for the ICAP Investigators. A randomized trial of colchicine for acute pericarditis. N Engl J Med 2013;369(16):1522-1528.

Study design

Randomized controlled trial (double-blinded)

Funding source

Government

Concealed

Setting

Inpatient (any location) with outpatient follow-up

Synopsis

Colchicine has been previously shown effective in the prevention of recurrent pericarditis (Daily POEM 12-16-2011). In this study, patients with a first episode of acute pericarditis were randomized to receive either colchicine (0.5 mg - 1 mg daily for 3 months; n = 120) or matching placebo (n = 120). All patients also received conventional treatment for acute pericarditis, either aspirin 800 mg or ibuprofen 600 mg every 8 hours for 7 to 10 days, followed by a taper, or (for those with contraindications to aspirin or ibuprofen) glucorticoid therapy for 2 weeks, followed by a taper. Baseline characteristics in the 2 groups were similar: mean age was 52 years, 60% were male, and the most common cause of pericarditis was idiopathic. The majority of patients received aspirin rather than ibuprofen or glucocorticoids as concomitant therapy. Adherence to the study drug was higher than 95% and did not differ between the 2 groups. Patients were followed up for a mean of 22 months and none were lost to follow-up. Analysis was by intention to treat. The primary outcome of incessant or recurrent pericarditis was decreased in the colchicine group as compared with the placebo group (16.7% vs 37.5%; relative risk = 0.56; 95% CI, 0.30-0.72; P < .001). In addition, the colchicine group had significantly better outcomes with regard to the number of patients with persistent symptoms at 72 hours (19% vs 40%), rate of remission within 1 week (85% vs 58%), time to first recurrence (25 weeks vs 18 weeks), and rate of percarditis-related hospitalizations (5% vs 14%). There was no difference in either overall side effects or gastrointestinal side effects between the 2 groups.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

Does the addition of colchicine improve outcomes in the treatment of an initial episode of acute pericarditis?

Bottom line

When used in addition to conventional anti-inflammatory therapy, colchicine decreases the rate of incessant or recurrent pericarditis. You would need to treat 4 patients with colchicine to prevent one such episode. (LOE = 1b)

Reference

Imazio M, Brucato A, Cemin R, et al, for the ICAP Investigators. A randomized trial of colchicine for acute pericarditis. N Engl J Med 2013;369(16):1522-1528.

Study design

Randomized controlled trial (double-blinded)

Funding source

Government

Concealed

Setting

Inpatient (any location) with outpatient follow-up

Synopsis

Colchicine has been previously shown effective in the prevention of recurrent pericarditis (Daily POEM 12-16-2011). In this study, patients with a first episode of acute pericarditis were randomized to receive either colchicine (0.5 mg - 1 mg daily for 3 months; n = 120) or matching placebo (n = 120). All patients also received conventional treatment for acute pericarditis, either aspirin 800 mg or ibuprofen 600 mg every 8 hours for 7 to 10 days, followed by a taper, or (for those with contraindications to aspirin or ibuprofen) glucorticoid therapy for 2 weeks, followed by a taper. Baseline characteristics in the 2 groups were similar: mean age was 52 years, 60% were male, and the most common cause of pericarditis was idiopathic. The majority of patients received aspirin rather than ibuprofen or glucocorticoids as concomitant therapy. Adherence to the study drug was higher than 95% and did not differ between the 2 groups. Patients were followed up for a mean of 22 months and none were lost to follow-up. Analysis was by intention to treat. The primary outcome of incessant or recurrent pericarditis was decreased in the colchicine group as compared with the placebo group (16.7% vs 37.5%; relative risk = 0.56; 95% CI, 0.30-0.72; P < .001). In addition, the colchicine group had significantly better outcomes with regard to the number of patients with persistent symptoms at 72 hours (19% vs 40%), rate of remission within 1 week (85% vs 58%), time to first recurrence (25 weeks vs 18 weeks), and rate of percarditis-related hospitalizations (5% vs 14%). There was no difference in either overall side effects or gastrointestinal side effects between the 2 groups.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

Does the addition of colchicine improve outcomes in the treatment of an initial episode of acute pericarditis?

Bottom line

When used in addition to conventional anti-inflammatory therapy, colchicine decreases the rate of incessant or recurrent pericarditis. You would need to treat 4 patients with colchicine to prevent one such episode. (LOE = 1b)

Reference

Imazio M, Brucato A, Cemin R, et al, for the ICAP Investigators. A randomized trial of colchicine for acute pericarditis. N Engl J Med 2013;369(16):1522-1528.

Study design

Randomized controlled trial (double-blinded)

Funding source

Government

Concealed

Setting

Inpatient (any location) with outpatient follow-up

Synopsis

Colchicine has been previously shown effective in the prevention of recurrent pericarditis (Daily POEM 12-16-2011). In this study, patients with a first episode of acute pericarditis were randomized to receive either colchicine (0.5 mg - 1 mg daily for 3 months; n = 120) or matching placebo (n = 120). All patients also received conventional treatment for acute pericarditis, either aspirin 800 mg or ibuprofen 600 mg every 8 hours for 7 to 10 days, followed by a taper, or (for those with contraindications to aspirin or ibuprofen) glucorticoid therapy for 2 weeks, followed by a taper. Baseline characteristics in the 2 groups were similar: mean age was 52 years, 60% were male, and the most common cause of pericarditis was idiopathic. The majority of patients received aspirin rather than ibuprofen or glucocorticoids as concomitant therapy. Adherence to the study drug was higher than 95% and did not differ between the 2 groups. Patients were followed up for a mean of 22 months and none were lost to follow-up. Analysis was by intention to treat. The primary outcome of incessant or recurrent pericarditis was decreased in the colchicine group as compared with the placebo group (16.7% vs 37.5%; relative risk = 0.56; 95% CI, 0.30-0.72; P < .001). In addition, the colchicine group had significantly better outcomes with regard to the number of patients with persistent symptoms at 72 hours (19% vs 40%), rate of remission within 1 week (85% vs 58%), time to first recurrence (25 weeks vs 18 weeks), and rate of percarditis-related hospitalizations (5% vs 14%). There was no difference in either overall side effects or gastrointestinal side effects between the 2 groups.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

Does the combination of prednisolone and pentoxifylline improve survival in patients with severe alcoholic hepatitis?

Bottom line

Although pentoxifylline and prednisolone have both been demonstrated to be effective individual treatments for alcoholic hepatitis, the combination of both did not improve survival more than prednisolone alone. (LOE = 1b)

Reference

Mathurin P, Louvet A, Duhamel A, et al. Prednisolone with vs without pentoxifylline and survival of patients with severe alcoholic hepatitis: A randomized clinical trial. JAMA 2013;310(10):1033-1041.

Study design

Randomized controlled trial (double-blinded)

Funding source

Government

Allocation

Concealed

Setting

Inpatient (any location) with outpatient follow-up

Synopsis

Current guidelines recommend the use of either prednisolone or pentoxifylline for the treatment of severe alcoholic hepatitis. The benefit of the combination of these 2 medications in this setting is unclear. These investigators enrolled patients who were current heavy alcohol users and who had biopsy-proven alcoholic hepatitis with a Maddrey score of 32 or more. Patients were randomized, using concealed allocation, to receive prednisolone 40 mg daily plus pentoxifylline 400 mg 3 times daily (n = 133) or prednisolone 40 mg daily plus placebo (n = 137). Treatment lasted for 28 days and follow-up was 100% at 6 months. The patients had a mean age of 51 years and an average Maddrey score in the 50s (indicating severe disease). No significant difference was detected in 6-month survival between the 2 groups in either the intention-to-treat or per-protocol analyses. Overall, there were 82 deaths in the cohort at 6 months -- 40 in the pentoxifylline-prednisolone group and 42 in the placebo-prednisolone group. The risk of hepatorenal syndrome was decreased at 1 month in the combination therapy group as compared with the placebo group (3.1% vs 11.7%; P = .007), but this difference did not remain significant at 6 months. It is important to note, however, that this study was not powered to detect a difference in the incidence of hepatorenal syndrome.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

Does the combination of prednisolone and pentoxifylline improve survival in patients with severe alcoholic hepatitis?

Bottom line

Although pentoxifylline and prednisolone have both been demonstrated to be effective individual treatments for alcoholic hepatitis, the combination of both did not improve survival more than prednisolone alone. (LOE = 1b)

Reference

Mathurin P, Louvet A, Duhamel A, et al. Prednisolone with vs without pentoxifylline and survival of patients with severe alcoholic hepatitis: A randomized clinical trial. JAMA 2013;310(10):1033-1041.

Study design

Randomized controlled trial (double-blinded)

Funding source

Government

Allocation

Concealed

Setting

Inpatient (any location) with outpatient follow-up

Synopsis

Current guidelines recommend the use of either prednisolone or pentoxifylline for the treatment of severe alcoholic hepatitis. The benefit of the combination of these 2 medications in this setting is unclear. These investigators enrolled patients who were current heavy alcohol users and who had biopsy-proven alcoholic hepatitis with a Maddrey score of 32 or more. Patients were randomized, using concealed allocation, to receive prednisolone 40 mg daily plus pentoxifylline 400 mg 3 times daily (n = 133) or prednisolone 40 mg daily plus placebo (n = 137). Treatment lasted for 28 days and follow-up was 100% at 6 months. The patients had a mean age of 51 years and an average Maddrey score in the 50s (indicating severe disease). No significant difference was detected in 6-month survival between the 2 groups in either the intention-to-treat or per-protocol analyses. Overall, there were 82 deaths in the cohort at 6 months -- 40 in the pentoxifylline-prednisolone group and 42 in the placebo-prednisolone group. The risk of hepatorenal syndrome was decreased at 1 month in the combination therapy group as compared with the placebo group (3.1% vs 11.7%; P = .007), but this difference did not remain significant at 6 months. It is important to note, however, that this study was not powered to detect a difference in the incidence of hepatorenal syndrome.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

Does the combination of prednisolone and pentoxifylline improve survival in patients with severe alcoholic hepatitis?

Bottom line

Although pentoxifylline and prednisolone have both been demonstrated to be effective individual treatments for alcoholic hepatitis, the combination of both did not improve survival more than prednisolone alone. (LOE = 1b)

Reference

Mathurin P, Louvet A, Duhamel A, et al. Prednisolone with vs without pentoxifylline and survival of patients with severe alcoholic hepatitis: A randomized clinical trial. JAMA 2013;310(10):1033-1041.

Study design

Randomized controlled trial (double-blinded)

Funding source

Government

Allocation

Concealed

Setting

Inpatient (any location) with outpatient follow-up

Synopsis

Current guidelines recommend the use of either prednisolone or pentoxifylline for the treatment of severe alcoholic hepatitis. The benefit of the combination of these 2 medications in this setting is unclear. These investigators enrolled patients who were current heavy alcohol users and who had biopsy-proven alcoholic hepatitis with a Maddrey score of 32 or more. Patients were randomized, using concealed allocation, to receive prednisolone 40 mg daily plus pentoxifylline 400 mg 3 times daily (n = 133) or prednisolone 40 mg daily plus placebo (n = 137). Treatment lasted for 28 days and follow-up was 100% at 6 months. The patients had a mean age of 51 years and an average Maddrey score in the 50s (indicating severe disease). No significant difference was detected in 6-month survival between the 2 groups in either the intention-to-treat or per-protocol analyses. Overall, there were 82 deaths in the cohort at 6 months -- 40 in the pentoxifylline-prednisolone group and 42 in the placebo-prednisolone group. The risk of hepatorenal syndrome was decreased at 1 month in the combination therapy group as compared with the placebo group (3.1% vs 11.7%; P = .007), but this difference did not remain significant at 6 months. It is important to note, however, that this study was not powered to detect a difference in the incidence of hepatorenal syndrome.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

Does preventive percutaneous coronary intervention of noninfarct but stenosed arteries improve outcomes in patients with acute ST-segment elevation myocardial infarction?

Bottom line

Preventive percutaneous coronary intervention (PCI) of noninfarct, stenosed arteries duing treatment for acute ST-segment elevation myocardial infarction (STEMI) is effective in decreasing long-term cardiovascular events. You would need to treat 7 patients with preventive PCI to avoid one such event. (LOE = 1b)

Reference

Wald DS, Morris JK, Wald NJ, et al, for the PRAMI Investigators. Randomized trial of preventive angioplasty in myocardial infarction. N Engl J Med 2013;369(12):1115-1123.

Study design

Randomized controlled trial (single-blinded)

Funding source

Foundation

Allocation

Concealed

Setting

Inpatient (any location) with outpatient follow-up

Synopsis

This study enrolled 465 patients with acute STEMI who received successful PCI to the infarct artery and were noted to have stenosis greater than 50% in other noninfarct coronary arteries during angiography. Patients with history of, or indications for, coronary artery bypass grafting and those in cardiogenic shock were excluded. Using concealed allocation, the investigators randomized patients to receive no further PCI or immediate preventive PCI to noninfarct arteries. The 2 groups had similar comorbidities and a mean age of 62 years. The use of drug-eluting stents and medical therapy after discharge were also similar between groups. The primary outcome was the composite of death from cardiac causes, nonfatal myocardial infarction, or refractory angina. Mean follow-up was 2 years and analysis was by intention to treat. The trial was stopped early because of highly significant results favoring preventive PCI. Overall, there was a 9% event rate in the preventive PCI group as compared with 23% in the other group (hazard ratio = 0.35; 95% CI, 0.21-0.58; P < .001). The individual components of the primary outcome showed similar results, although the reduction in cardiac death was not statistically significant (P = .07). As expected, the procedure time and contrast volume used were higher in the preventive PCI group, but the complication rates, including contrast-induced nephropathy, did not differ between groups.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

Does preventive percutaneous coronary intervention of noninfarct but stenosed arteries improve outcomes in patients with acute ST-segment elevation myocardial infarction?

Bottom line

Preventive percutaneous coronary intervention (PCI) of noninfarct, stenosed arteries duing treatment for acute ST-segment elevation myocardial infarction (STEMI) is effective in decreasing long-term cardiovascular events. You would need to treat 7 patients with preventive PCI to avoid one such event. (LOE = 1b)

Reference

Wald DS, Morris JK, Wald NJ, et al, for the PRAMI Investigators. Randomized trial of preventive angioplasty in myocardial infarction. N Engl J Med 2013;369(12):1115-1123.

Study design

Randomized controlled trial (single-blinded)

Funding source

Foundation

Allocation

Concealed

Setting

Inpatient (any location) with outpatient follow-up

Synopsis

This study enrolled 465 patients with acute STEMI who received successful PCI to the infarct artery and were noted to have stenosis greater than 50% in other noninfarct coronary arteries during angiography. Patients with history of, or indications for, coronary artery bypass grafting and those in cardiogenic shock were excluded. Using concealed allocation, the investigators randomized patients to receive no further PCI or immediate preventive PCI to noninfarct arteries. The 2 groups had similar comorbidities and a mean age of 62 years. The use of drug-eluting stents and medical therapy after discharge were also similar between groups. The primary outcome was the composite of death from cardiac causes, nonfatal myocardial infarction, or refractory angina. Mean follow-up was 2 years and analysis was by intention to treat. The trial was stopped early because of highly significant results favoring preventive PCI. Overall, there was a 9% event rate in the preventive PCI group as compared with 23% in the other group (hazard ratio = 0.35; 95% CI, 0.21-0.58; P < .001). The individual components of the primary outcome showed similar results, although the reduction in cardiac death was not statistically significant (P = .07). As expected, the procedure time and contrast volume used were higher in the preventive PCI group, but the complication rates, including contrast-induced nephropathy, did not differ between groups.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

Does preventive percutaneous coronary intervention of noninfarct but stenosed arteries improve outcomes in patients with acute ST-segment elevation myocardial infarction?

Bottom line

Preventive percutaneous coronary intervention (PCI) of noninfarct, stenosed arteries duing treatment for acute ST-segment elevation myocardial infarction (STEMI) is effective in decreasing long-term cardiovascular events. You would need to treat 7 patients with preventive PCI to avoid one such event. (LOE = 1b)

Reference

Wald DS, Morris JK, Wald NJ, et al, for the PRAMI Investigators. Randomized trial of preventive angioplasty in myocardial infarction. N Engl J Med 2013;369(12):1115-1123.

Study design

Randomized controlled trial (single-blinded)

Funding source

Foundation

Allocation

Concealed

Setting

Inpatient (any location) with outpatient follow-up

Synopsis

This study enrolled 465 patients with acute STEMI who received successful PCI to the infarct artery and were noted to have stenosis greater than 50% in other noninfarct coronary arteries during angiography. Patients with history of, or indications for, coronary artery bypass grafting and those in cardiogenic shock were excluded. Using concealed allocation, the investigators randomized patients to receive no further PCI or immediate preventive PCI to noninfarct arteries. The 2 groups had similar comorbidities and a mean age of 62 years. The use of drug-eluting stents and medical therapy after discharge were also similar between groups. The primary outcome was the composite of death from cardiac causes, nonfatal myocardial infarction, or refractory angina. Mean follow-up was 2 years and analysis was by intention to treat. The trial was stopped early because of highly significant results favoring preventive PCI. Overall, there was a 9% event rate in the preventive PCI group as compared with 23% in the other group (hazard ratio = 0.35; 95% CI, 0.21-0.58; P < .001). The individual components of the primary outcome showed similar results, although the reduction in cardiac death was not statistically significant (P = .07). As expected, the procedure time and contrast volume used were higher in the preventive PCI group, but the complication rates, including contrast-induced nephropathy, did not differ between groups.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

Does implementation of the I COUGH strategy improve pulmonary outcomes in postoperative patients?

Bottom line

Although not statistically significant, data from this before-and-after trial shows that the I COUGH strategy (emphasizing lung expansion, early mobilization, oral hygiene, and patient and provider education) may decrease postoperative pulmonary complications in hospitalized patients. (LOE = 2c)

Reference

Cassidy MR, Rosenkranz P, McCabe K, Rosen JE, McAneny D. I COUGH: Reducing postoperative pulmonary complications with a multidisciplinary patient care program. JAMA Surg 2013;148(8):740-745.

Study design

Other

Funding source

Unknown/not stated

Allocation

Uncertain

Setting

Inpatient (any location)

Synopsis

Data from the National Surgical Quality Improvement Program (NQSIP) showed that the Boston Medical Center was a high outlier for postoperative pulmonary complications. To address this, a pulmonary care working group including surgeons, internists, nurses, and respiratory therapists was formed. The group reviewed the literature on preventing postoperative pulmonary complications and devised the I COUGH strategy: (1) Incentive spirometry, (2) Coughing and deep breathing, (3) Oral care, (4) Understanding (patient and family education), (5) Getting out of bed, and (6) Head-of-bed elevation. Postoperative pain control was also emphasized. Educational materials including videos and brochures were developed for patients and families and distributed in surgery and perioperative clinics. Incentive spirometry technique was taught and reinforced in the preoperative setting. Frontline nurses and physicians also received education regarding the baseline outcomes data and the reasons for developing the program. Finally, standardized order sets outlining the components of I COUGH were created. The I COUGH strategy was implemented for all hospitalized general and vascular surgery patients in the institution. More patients were out of bed postintervention than preintervention (70% vs 20%; P < .001). Similarly, more patients had incentive spirometry available and within reach postintervention (77% vs 53%; P < .001). Note, however, that the preintervention audits were unannounced observations of nursing practices whereas postintervention audits were by review of nursing documentation only. Although not statistically significant, the NSQIP data revealed trends toward decreased incidences of postoperative pneumonia (2.6% vs 1.6%; P = .09) and unplanned intubations (2.0% vs 1.2%; P = .09) after I COUGH implementation. National averages for postoperative pneumonias and unplanned intubations for comparable hospitals during this period were 1.4% to 1.7% and 1.4% to 1.6%, respectively.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

Does implementation of the I COUGH strategy improve pulmonary outcomes in postoperative patients?

Bottom line

Although not statistically significant, data from this before-and-after trial shows that the I COUGH strategy (emphasizing lung expansion, early mobilization, oral hygiene, and patient and provider education) may decrease postoperative pulmonary complications in hospitalized patients. (LOE = 2c)

Reference

Cassidy MR, Rosenkranz P, McCabe K, Rosen JE, McAneny D. I COUGH: Reducing postoperative pulmonary complications with a multidisciplinary patient care program. JAMA Surg 2013;148(8):740-745.

Study design

Other

Funding source

Unknown/not stated

Allocation

Uncertain

Setting

Inpatient (any location)

Synopsis

Data from the National Surgical Quality Improvement Program (NQSIP) showed that the Boston Medical Center was a high outlier for postoperative pulmonary complications. To address this, a pulmonary care working group including surgeons, internists, nurses, and respiratory therapists was formed. The group reviewed the literature on preventing postoperative pulmonary complications and devised the I COUGH strategy: (1) Incentive spirometry, (2) Coughing and deep breathing, (3) Oral care, (4) Understanding (patient and family education), (5) Getting out of bed, and (6) Head-of-bed elevation. Postoperative pain control was also emphasized. Educational materials including videos and brochures were developed for patients and families and distributed in surgery and perioperative clinics. Incentive spirometry technique was taught and reinforced in the preoperative setting. Frontline nurses and physicians also received education regarding the baseline outcomes data and the reasons for developing the program. Finally, standardized order sets outlining the components of I COUGH were created. The I COUGH strategy was implemented for all hospitalized general and vascular surgery patients in the institution. More patients were out of bed postintervention than preintervention (70% vs 20%; P < .001). Similarly, more patients had incentive spirometry available and within reach postintervention (77% vs 53%; P < .001). Note, however, that the preintervention audits were unannounced observations of nursing practices whereas postintervention audits were by review of nursing documentation only. Although not statistically significant, the NSQIP data revealed trends toward decreased incidences of postoperative pneumonia (2.6% vs 1.6%; P = .09) and unplanned intubations (2.0% vs 1.2%; P = .09) after I COUGH implementation. National averages for postoperative pneumonias and unplanned intubations for comparable hospitals during this period were 1.4% to 1.7% and 1.4% to 1.6%, respectively.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

Does implementation of the I COUGH strategy improve pulmonary outcomes in postoperative patients?

Bottom line

Although not statistically significant, data from this before-and-after trial shows that the I COUGH strategy (emphasizing lung expansion, early mobilization, oral hygiene, and patient and provider education) may decrease postoperative pulmonary complications in hospitalized patients. (LOE = 2c)

Reference

Cassidy MR, Rosenkranz P, McCabe K, Rosen JE, McAneny D. I COUGH: Reducing postoperative pulmonary complications with a multidisciplinary patient care program. JAMA Surg 2013;148(8):740-745.

Study design

Other

Funding source

Unknown/not stated

Allocation

Uncertain

Setting

Inpatient (any location)

Synopsis

Data from the National Surgical Quality Improvement Program (NQSIP) showed that the Boston Medical Center was a high outlier for postoperative pulmonary complications. To address this, a pulmonary care working group including surgeons, internists, nurses, and respiratory therapists was formed. The group reviewed the literature on preventing postoperative pulmonary complications and devised the I COUGH strategy: (1) Incentive spirometry, (2) Coughing and deep breathing, (3) Oral care, (4) Understanding (patient and family education), (5) Getting out of bed, and (6) Head-of-bed elevation. Postoperative pain control was also emphasized. Educational materials including videos and brochures were developed for patients and families and distributed in surgery and perioperative clinics. Incentive spirometry technique was taught and reinforced in the preoperative setting. Frontline nurses and physicians also received education regarding the baseline outcomes data and the reasons for developing the program. Finally, standardized order sets outlining the components of I COUGH were created. The I COUGH strategy was implemented for all hospitalized general and vascular surgery patients in the institution. More patients were out of bed postintervention than preintervention (70% vs 20%; P < .001). Similarly, more patients had incentive spirometry available and within reach postintervention (77% vs 53%; P < .001). Note, however, that the preintervention audits were unannounced observations of nursing practices whereas postintervention audits were by review of nursing documentation only. Although not statistically significant, the NSQIP data revealed trends toward decreased incidences of postoperative pneumonia (2.6% vs 1.6%; P = .09) and unplanned intubations (2.0% vs 1.2%; P = .09) after I COUGH implementation. National averages for postoperative pneumonias and unplanned intubations for comparable hospitals during this period were 1.4% to 1.7% and 1.4% to 1.6%, respectively.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

How effective is intensive smoking cessation support for hospitalized patients?

Bottom line

Therapy provided by highly trained smoking cessation practitioners, combined with pharmacotherapy and community support referrals upon discharge, may increase short-term quit rates among hospitalized smokers. However, this effect did not persist at 6 months. Moreover, this study did not address the cost-effectiveness of such an intensive strategy. (LOE = 1b-)

Reference

Murray RL, Leonardi-Bee J, Marsh J, et al. Systematic identification and treatment of smokers by hospital based cessation practitioners in a secondary care setting: cluster randomised controlled trial. BMJ 2013;347:f4004.

Study design

Randomized controlled trial (nonblinded)

Funding source

Government

Allocation

Concealed

Setting

Inpatient (any location) with outpatient follow-up

Synopsis

Investigators at a large teaching hospital in the United Kingdom randomized 18 medical wards, using concealed allocation, to deliver either usual care for smoking cessation or the intervention strategy. Almost 500 patients were enrolled in the study and received smoking cessation treatment based on the allocation of their admission ward. The intervention consisted of identification of smokers upon admission, followed by delivery of smoking advice and offer of cessation support. Patients who accepted the support received daily in-hospital counseling by a trained smoking cessation practitioner. Initial sessions lasted 20 minutes to 30 minutes; subsequent sessions were 10 minutes long. Patients were also prescribed dual nicotine replacement therapy (transdermal patch plus either gum, lozenge, or nasal spray) or varenicline therapy, if preferred. Additionally, intervention patients received referrals to community cessation support services upon discharge. Patients on the usual care ward received cessation advice and support according to the usual practices of the providers involved in their care. The intervention group patients were younger and more likely to be male. Additionally, because of randomization by admission ward, the majority of intervention patients came from cardiac wards, whereas the majority of usual care patients came from respiratory wards. Finally, many eligible oncology patients were not included in the trial because of their doctors’ reluctance to have the study team approach these terminally ill patients. All patients in the intervention group received advice to quit compared with less than half of the patients in the usual care group. The use of pharmacotherapy and cessation support therapy, both in the hospital and upon discharge, was greater in the intervention group. The quit rate at 4 weeks, defined as self-reported smoking cessation validated by exhaled carbon monoxide measurement, favored the intervention group (38% vs 17%; P = .06), but did not quite reach statistical significance. When oncology patients (n = 45) were excluded from the analysis retrospectively, however, the result was significant (42% quit rate in the intervention group vs 17% in the usual care group; P = .006). Six-month cessation rates, though also higher in the intervention group, were not statistically different (19% vs 9%; P = .37).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

How effective is intensive smoking cessation support for hospitalized patients?

Bottom line

Therapy provided by highly trained smoking cessation practitioners, combined with pharmacotherapy and community support referrals upon discharge, may increase short-term quit rates among hospitalized smokers. However, this effect did not persist at 6 months. Moreover, this study did not address the cost-effectiveness of such an intensive strategy. (LOE = 1b-)

Reference

Murray RL, Leonardi-Bee J, Marsh J, et al. Systematic identification and treatment of smokers by hospital based cessation practitioners in a secondary care setting: cluster randomised controlled trial. BMJ 2013;347:f4004.

Study design

Randomized controlled trial (nonblinded)

Funding source

Government

Allocation

Concealed

Setting

Inpatient (any location) with outpatient follow-up

Synopsis

Investigators at a large teaching hospital in the United Kingdom randomized 18 medical wards, using concealed allocation, to deliver either usual care for smoking cessation or the intervention strategy. Almost 500 patients were enrolled in the study and received smoking cessation treatment based on the allocation of their admission ward. The intervention consisted of identification of smokers upon admission, followed by delivery of smoking advice and offer of cessation support. Patients who accepted the support received daily in-hospital counseling by a trained smoking cessation practitioner. Initial sessions lasted 20 minutes to 30 minutes; subsequent sessions were 10 minutes long. Patients were also prescribed dual nicotine replacement therapy (transdermal patch plus either gum, lozenge, or nasal spray) or varenicline therapy, if preferred. Additionally, intervention patients received referrals to community cessation support services upon discharge. Patients on the usual care ward received cessation advice and support according to the usual practices of the providers involved in their care. The intervention group patients were younger and more likely to be male. Additionally, because of randomization by admission ward, the majority of intervention patients came from cardiac wards, whereas the majority of usual care patients came from respiratory wards. Finally, many eligible oncology patients were not included in the trial because of their doctors’ reluctance to have the study team approach these terminally ill patients. All patients in the intervention group received advice to quit compared with less than half of the patients in the usual care group. The use of pharmacotherapy and cessation support therapy, both in the hospital and upon discharge, was greater in the intervention group. The quit rate at 4 weeks, defined as self-reported smoking cessation validated by exhaled carbon monoxide measurement, favored the intervention group (38% vs 17%; P = .06), but did not quite reach statistical significance. When oncology patients (n = 45) were excluded from the analysis retrospectively, however, the result was significant (42% quit rate in the intervention group vs 17% in the usual care group; P = .006). Six-month cessation rates, though also higher in the intervention group, were not statistically different (19% vs 9%; P = .37).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

How effective is intensive smoking cessation support for hospitalized patients?

Bottom line

Therapy provided by highly trained smoking cessation practitioners, combined with pharmacotherapy and community support referrals upon discharge, may increase short-term quit rates among hospitalized smokers. However, this effect did not persist at 6 months. Moreover, this study did not address the cost-effectiveness of such an intensive strategy. (LOE = 1b-)

Reference

Murray RL, Leonardi-Bee J, Marsh J, et al. Systematic identification and treatment of smokers by hospital based cessation practitioners in a secondary care setting: cluster randomised controlled trial. BMJ 2013;347:f4004.

Study design

Randomized controlled trial (nonblinded)

Funding source

Government

Allocation

Concealed

Setting

Inpatient (any location) with outpatient follow-up

Synopsis

Investigators at a large teaching hospital in the United Kingdom randomized 18 medical wards, using concealed allocation, to deliver either usual care for smoking cessation or the intervention strategy. Almost 500 patients were enrolled in the study and received smoking cessation treatment based on the allocation of their admission ward. The intervention consisted of identification of smokers upon admission, followed by delivery of smoking advice and offer of cessation support. Patients who accepted the support received daily in-hospital counseling by a trained smoking cessation practitioner. Initial sessions lasted 20 minutes to 30 minutes; subsequent sessions were 10 minutes long. Patients were also prescribed dual nicotine replacement therapy (transdermal patch plus either gum, lozenge, or nasal spray) or varenicline therapy, if preferred. Additionally, intervention patients received referrals to community cessation support services upon discharge. Patients on the usual care ward received cessation advice and support according to the usual practices of the providers involved in their care. The intervention group patients were younger and more likely to be male. Additionally, because of randomization by admission ward, the majority of intervention patients came from cardiac wards, whereas the majority of usual care patients came from respiratory wards. Finally, many eligible oncology patients were not included in the trial because of their doctors’ reluctance to have the study team approach these terminally ill patients. All patients in the intervention group received advice to quit compared with less than half of the patients in the usual care group. The use of pharmacotherapy and cessation support therapy, both in the hospital and upon discharge, was greater in the intervention group. The quit rate at 4 weeks, defined as self-reported smoking cessation validated by exhaled carbon monoxide measurement, favored the intervention group (38% vs 17%; P = .06), but did not quite reach statistical significance. When oncology patients (n = 45) were excluded from the analysis retrospectively, however, the result was significant (42% quit rate in the intervention group vs 17% in the usual care group; P = .006). Six-month cessation rates, though also higher in the intervention group, were not statistically different (19% vs 9%; P = .37).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

For patients presenting with acute ischemic stroke, is earlier onset of thrombolytic therapy associated with better outcomes?

Bottom line

Earlier thrombolytic therapy in patients with acute ischemic stroke is associated with improved outcomes, including reduced inpatient mortality, fewer intracranial bleeds, higher rates of independent ambulation at discharge, and increased number of discharges to home. These findings support continued efforts to accelerate the process of acute stroke care delivery and to promote earlier patient presentation after stroke symptom onset. (LOE = 2b)

Reference

Saver JL, Fonarow GC, Smith EE, et al. Time to treatment with intravenous tissue plasminogen activator and outcome from acute ischemic stroke. JAMA 2013;309(23):2480-2488.

Study design

Cohort (retrospective)

Funding source

Industry

Allocation

Uncertain

Setting

Inpatient (any location)

Synopsis

Previous data from 8 clinical trials of almost 2000 patients suggests that earlier thrombolytic therapy for ischemic stroke is most beneficial. The authors of the current study aimed to confirm the generalizability of these findings in patients treated for stroke in routine clinical practice. Using data from the American Heart Association's Get with the Guidelines stroke registry, these investigators examined the association between onset to treatment (OTT) time with intravenous tissue-type plasminogen activator (tPA) and outcomes for patients presenting with acute ischemic stroke. Almost 60,000 patients who received tPA within the guideline-recommended maximum of 4.5 hours of symptom onset were included in the analysis. Of this group, the median age was 72 years, 50% were women, and the median OTT time was 144 minutes. OTT times were further subdivided into 0 to 90-minute, 91- to 180-minute, and 181- to 270-minute intervals. Overall, 77% of the patients had an OTT time within 91 to 180 minutes while14% were treated between 181 and 270 minutes and 9% were treated within 90 minutes. Patients with earlier OTT times had higher stroke severity, were more likely to arrive by emergency medical service transport, and were more likely to present during regular weekday hours. Hospitals with higher volumes of tPA cases also had earlier OTT times. Out of the total study population, 33% were walking independently at discharge and almost 40% were discharged to home; 9% died in the hospital prior to discharge and 5% experienced intracranial bleeds. After adjusting for patient factors including stroke severity and hospital factors including volume of tPA-treated patients, the authors noted that earlier OTT times were associated with better outcomes. Among 1000 patients, every 15-minute-faster interval of treatment resulted in 8 more patients walking independently at discharge, 7 more patients being discharged to home, and 4 fewer patients dying in the hospital. Additionally, for every 15-minute decrease in OTT, bleeding events such as symptomatic intracranial bleeds and serious systemic bleeds were less likely to occur.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

For patients presenting with acute ischemic stroke, is earlier onset of thrombolytic therapy associated with better outcomes?

Bottom line

Earlier thrombolytic therapy in patients with acute ischemic stroke is associated with improved outcomes, including reduced inpatient mortality, fewer intracranial bleeds, higher rates of independent ambulation at discharge, and increased number of discharges to home. These findings support continued efforts to accelerate the process of acute stroke care delivery and to promote earlier patient presentation after stroke symptom onset. (LOE = 2b)

Reference

Saver JL, Fonarow GC, Smith EE, et al. Time to treatment with intravenous tissue plasminogen activator and outcome from acute ischemic stroke. JAMA 2013;309(23):2480-2488.

Study design

Cohort (retrospective)

Funding source

Industry

Allocation

Uncertain

Setting

Inpatient (any location)

Synopsis

Previous data from 8 clinical trials of almost 2000 patients suggests that earlier thrombolytic therapy for ischemic stroke is most beneficial. The authors of the current study aimed to confirm the generalizability of these findings in patients treated for stroke in routine clinical practice. Using data from the American Heart Association's Get with the Guidelines stroke registry, these investigators examined the association between onset to treatment (OTT) time with intravenous tissue-type plasminogen activator (tPA) and outcomes for patients presenting with acute ischemic stroke. Almost 60,000 patients who received tPA within the guideline-recommended maximum of 4.5 hours of symptom onset were included in the analysis. Of this group, the median age was 72 years, 50% were women, and the median OTT time was 144 minutes. OTT times were further subdivided into 0 to 90-minute, 91- to 180-minute, and 181- to 270-minute intervals. Overall, 77% of the patients had an OTT time within 91 to 180 minutes while14% were treated between 181 and 270 minutes and 9% were treated within 90 minutes. Patients with earlier OTT times had higher stroke severity, were more likely to arrive by emergency medical service transport, and were more likely to present during regular weekday hours. Hospitals with higher volumes of tPA cases also had earlier OTT times. Out of the total study population, 33% were walking independently at discharge and almost 40% were discharged to home; 9% died in the hospital prior to discharge and 5% experienced intracranial bleeds. After adjusting for patient factors including stroke severity and hospital factors including volume of tPA-treated patients, the authors noted that earlier OTT times were associated with better outcomes. Among 1000 patients, every 15-minute-faster interval of treatment resulted in 8 more patients walking independently at discharge, 7 more patients being discharged to home, and 4 fewer patients dying in the hospital. Additionally, for every 15-minute decrease in OTT, bleeding events such as symptomatic intracranial bleeds and serious systemic bleeds were less likely to occur.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

For patients presenting with acute ischemic stroke, is earlier onset of thrombolytic therapy associated with better outcomes?

Bottom line

Earlier thrombolytic therapy in patients with acute ischemic stroke is associated with improved outcomes, including reduced inpatient mortality, fewer intracranial bleeds, higher rates of independent ambulation at discharge, and increased number of discharges to home. These findings support continued efforts to accelerate the process of acute stroke care delivery and to promote earlier patient presentation after stroke symptom onset. (LOE = 2b)

Reference

Saver JL, Fonarow GC, Smith EE, et al. Time to treatment with intravenous tissue plasminogen activator and outcome from acute ischemic stroke. JAMA 2013;309(23):2480-2488.

Study design

Cohort (retrospective)

Funding source

Industry

Allocation

Uncertain

Setting

Inpatient (any location)

Synopsis

Previous data from 8 clinical trials of almost 2000 patients suggests that earlier thrombolytic therapy for ischemic stroke is most beneficial. The authors of the current study aimed to confirm the generalizability of these findings in patients treated for stroke in routine clinical practice. Using data from the American Heart Association's Get with the Guidelines stroke registry, these investigators examined the association between onset to treatment (OTT) time with intravenous tissue-type plasminogen activator (tPA) and outcomes for patients presenting with acute ischemic stroke. Almost 60,000 patients who received tPA within the guideline-recommended maximum of 4.5 hours of symptom onset were included in the analysis. Of this group, the median age was 72 years, 50% were women, and the median OTT time was 144 minutes. OTT times were further subdivided into 0 to 90-minute, 91- to 180-minute, and 181- to 270-minute intervals. Overall, 77% of the patients had an OTT time within 91 to 180 minutes while14% were treated between 181 and 270 minutes and 9% were treated within 90 minutes. Patients with earlier OTT times had higher stroke severity, were more likely to arrive by emergency medical service transport, and were more likely to present during regular weekday hours. Hospitals with higher volumes of tPA cases also had earlier OTT times. Out of the total study population, 33% were walking independently at discharge and almost 40% were discharged to home; 9% died in the hospital prior to discharge and 5% experienced intracranial bleeds. After adjusting for patient factors including stroke severity and hospital factors including volume of tPA-treated patients, the authors noted that earlier OTT times were associated with better outcomes. Among 1000 patients, every 15-minute-faster interval of treatment resulted in 8 more patients walking independently at discharge, 7 more patients being discharged to home, and 4 fewer patients dying in the hospital. Additionally, for every 15-minute decrease in OTT, bleeding events such as symptomatic intracranial bleeds and serious systemic bleeds were less likely to occur.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

Is aspirin as effective as dalteparin for extended venous thromboembolism prophylaxis in patients who have undergone total hip arthroplasty?

Bottom line

Aspirin is as effective as dalteparin for extended thromboprophylaxis in patients who had hip arthroplasty (THA) and had initially received 10 days of dalteparin prophylaxis postoperatively. Because of its relative safety, low cost, and easy administration, aspirin is an attractive alternative to low-molecular-weight heparin (LMWH) when used for this purpose. (LOE = 1b)

Reference

Anderson DR, Dunbar MJ, Bohm ER, et al. Aspirin versus low-molecular-weight heparin for extended venous thromboembolism prophylaxis after total hip arthroplasty. Ann Intern Med 2013;158(11):800-806.

Study design

Randomized controlled trial (double-blinded)

Funding source

Industry

Allocation

Concealed

Setting

Inpatient (any location) with outpatient follow-up

Synopsis

Previous studies have confirmed the benefit of extended thromboprophylaxis with LMWH in patients who have undergone elective THA (EBMG Evidence Summary 3/20/2003). The cost of LMWH and the inconvenience of administering daily subcutaneous injections are high, however. In this study, investigators enrolled patients undergoing elective THA to receive extended thromboprophylaxis with either LMWH, specifically dalteparin, or aspirin. All patients received an initial 8 days to 10 days of postoperative dalteparin prophylaxis. This was followed by randomization to either dalteparin 5000 units daily or aspirin 81 mg daily for the next 28 days. To preserve masking, placebo aspirin tablets and placebo dalteparin injections were also administered. Patients with metastatic cancer or those with conditions that precluded the use of an anticoagulant or aspirin were excluded. An amendment to the initial study protocol allowed patients using long-term aspirin therapy at a dose of less than 100 mg daily to be enrolled. These patients were assigned to either dalteparin or aspirin 81 mg in addition to their usual dose of aspirin. Because of slow recruitment, study enrollment was halted prematurely after 786 patients of a targeted group of 1100 had entered. Baseline characteristics in the 2 groups were similar, with a mean age of 58 years and mean hospital length of stay of 5 days. More than 90% of the patients in the study reported adherence to all doses of the study medications. After a 90-day follow-up period, aspirin was found to be as effective as dalteparin for the prevention of symptomatic venous thromboembolism (1.3% with venous thromboembolism events in the dalteparin group, 0.3% in the aspirin group; P < .001 for noninferiority). There were no differences in clinically significant bleeding events between the 2 groups, although the trend favored aspirin (1.3% with dalteparin vs 0.5% with aspirin). In the subset of patients using long-term aspirin therapy (n = 39), one patient assigned to the aspirin group had a clinically significant, nonmajor bleeding event, but there were no venous thromboembolism events in either group.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

Is aspirin as effective as dalteparin for extended venous thromboembolism prophylaxis in patients who have undergone total hip arthroplasty?

Bottom line

Aspirin is as effective as dalteparin for extended thromboprophylaxis in patients who had hip arthroplasty (THA) and had initially received 10 days of dalteparin prophylaxis postoperatively. Because of its relative safety, low cost, and easy administration, aspirin is an attractive alternative to low-molecular-weight heparin (LMWH) when used for this purpose. (LOE = 1b)

Reference

Anderson DR, Dunbar MJ, Bohm ER, et al. Aspirin versus low-molecular-weight heparin for extended venous thromboembolism prophylaxis after total hip arthroplasty. Ann Intern Med 2013;158(11):800-806.

Study design

Randomized controlled trial (double-blinded)

Funding source

Industry

Allocation

Concealed

Setting

Inpatient (any location) with outpatient follow-up

Synopsis

Previous studies have confirmed the benefit of extended thromboprophylaxis with LMWH in patients who have undergone elective THA (EBMG Evidence Summary 3/20/2003). The cost of LMWH and the inconvenience of administering daily subcutaneous injections are high, however. In this study, investigators enrolled patients undergoing elective THA to receive extended thromboprophylaxis with either LMWH, specifically dalteparin, or aspirin. All patients received an initial 8 days to 10 days of postoperative dalteparin prophylaxis. This was followed by randomization to either dalteparin 5000 units daily or aspirin 81 mg daily for the next 28 days. To preserve masking, placebo aspirin tablets and placebo dalteparin injections were also administered. Patients with metastatic cancer or those with conditions that precluded the use of an anticoagulant or aspirin were excluded. An amendment to the initial study protocol allowed patients using long-term aspirin therapy at a dose of less than 100 mg daily to be enrolled. These patients were assigned to either dalteparin or aspirin 81 mg in addition to their usual dose of aspirin. Because of slow recruitment, study enrollment was halted prematurely after 786 patients of a targeted group of 1100 had entered. Baseline characteristics in the 2 groups were similar, with a mean age of 58 years and mean hospital length of stay of 5 days. More than 90% of the patients in the study reported adherence to all doses of the study medications. After a 90-day follow-up period, aspirin was found to be as effective as dalteparin for the prevention of symptomatic venous thromboembolism (1.3% with venous thromboembolism events in the dalteparin group, 0.3% in the aspirin group; P < .001 for noninferiority). There were no differences in clinically significant bleeding events between the 2 groups, although the trend favored aspirin (1.3% with dalteparin vs 0.5% with aspirin). In the subset of patients using long-term aspirin therapy (n = 39), one patient assigned to the aspirin group had a clinically significant, nonmajor bleeding event, but there were no venous thromboembolism events in either group.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

Is aspirin as effective as dalteparin for extended venous thromboembolism prophylaxis in patients who have undergone total hip arthroplasty?

Bottom line

Aspirin is as effective as dalteparin for extended thromboprophylaxis in patients who had hip arthroplasty (THA) and had initially received 10 days of dalteparin prophylaxis postoperatively. Because of its relative safety, low cost, and easy administration, aspirin is an attractive alternative to low-molecular-weight heparin (LMWH) when used for this purpose. (LOE = 1b)

Reference

Anderson DR, Dunbar MJ, Bohm ER, et al. Aspirin versus low-molecular-weight heparin for extended venous thromboembolism prophylaxis after total hip arthroplasty. Ann Intern Med 2013;158(11):800-806.

Study design

Randomized controlled trial (double-blinded)

Funding source

Industry

Allocation

Concealed

Setting

Inpatient (any location) with outpatient follow-up

Synopsis

Previous studies have confirmed the benefit of extended thromboprophylaxis with LMWH in patients who have undergone elective THA (EBMG Evidence Summary 3/20/2003). The cost of LMWH and the inconvenience of administering daily subcutaneous injections are high, however. In this study, investigators enrolled patients undergoing elective THA to receive extended thromboprophylaxis with either LMWH, specifically dalteparin, or aspirin. All patients received an initial 8 days to 10 days of postoperative dalteparin prophylaxis. This was followed by randomization to either dalteparin 5000 units daily or aspirin 81 mg daily for the next 28 days. To preserve masking, placebo aspirin tablets and placebo dalteparin injections were also administered. Patients with metastatic cancer or those with conditions that precluded the use of an anticoagulant or aspirin were excluded. An amendment to the initial study protocol allowed patients using long-term aspirin therapy at a dose of less than 100 mg daily to be enrolled. These patients were assigned to either dalteparin or aspirin 81 mg in addition to their usual dose of aspirin. Because of slow recruitment, study enrollment was halted prematurely after 786 patients of a targeted group of 1100 had entered. Baseline characteristics in the 2 groups were similar, with a mean age of 58 years and mean hospital length of stay of 5 days. More than 90% of the patients in the study reported adherence to all doses of the study medications. After a 90-day follow-up period, aspirin was found to be as effective as dalteparin for the prevention of symptomatic venous thromboembolism (1.3% with venous thromboembolism events in the dalteparin group, 0.3% in the aspirin group; P < .001 for noninferiority). There were no differences in clinically significant bleeding events between the 2 groups, although the trend favored aspirin (1.3% with dalteparin vs 0.5% with aspirin). In the subset of patients using long-term aspirin therapy (n = 39), one patient assigned to the aspirin group had a clinically significant, nonmajor bleeding event, but there were no venous thromboembolism events in either group.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.